{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T02:00:54Z","timestamp":1789696854747,"version":"4.0.1"},"reference-count":118,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Ketones not only act as metabolic fuel for the brain in periods of carbohydrate shortage, but also serve as signalling molecules that improve cognition. Ketogenic states can be induced peripherally by physiological interventions such as fasting and exercise, or ketogenic diets\/exogenous supplementation. These interventions beneficially act on the brain through partially overlapping peripheral metabolic pathways. We focus on the role of peripheral organs such as the intestine, liver and skeletal muscle in mediating cognitive benefits in response to these interventions and discuss the prominent roles of the nuclear receptor peroxisome proliferator\u2010activated receptor \u03b4, which serves as a nutrient sensor guiding ketones to the brain, where they stimulate the multifunctional cognition\u2010improving factor, brain\u2010derived neurotrophic factor.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16703-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1113\/jp287462","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T03:33:24Z","timestamp":1746416004000},"page":"2430-2447","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The central benefit of physiologically induced ketogenic states"],"prefix":"10.1113","volume":"604","author":[{"given":"Antonia","family":"Giacco","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Universit\u00e0 Degli Studi del Sannio Via De Sanctis Benevento Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Petito","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche Universit\u00e0 Degli Studi Della Campania \u2018Luigi Vanvitelli Via Vivaldi Caserta Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1571-0980","authenticated-orcid":false,"given":"Rosalba","family":"Senese","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche Universit\u00e0 Degli Studi Della Campania \u2018Luigi Vanvitelli Via Vivaldi Caserta Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Moreno","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Universit\u00e0 Degli Studi del Sannio Via De Sanctis Benevento Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assunta","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Dipartimento di Biologia Universit\u00e0 Degli Studi di Napoli \u2018Federico II,\u2019 Monte Sant'Angelo Universit\u00e0 degli Studi di Napoli \u2018Federico II,\u2019 Monte Sant'Angelo Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5797-0348","authenticated-orcid":false,"given":"Antonia","family":"Lanni","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche Universit\u00e0 Degli Studi Della Campania \u2018Luigi Vanvitelli Via Vivaldi Caserta Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5256-3599","authenticated-orcid":false,"given":"Pieter","family":"de Lange","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche Universit\u00e0 Degli Studi Della Campania \u2018Luigi Vanvitelli Via Vivaldi Caserta Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,5]]},"reference":[{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101593"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2011.09.005"},{"issue":"1","key":"e_1_2_2_4_1","article-title":"Effects of aerobic exercise on thyroid hormonal change responses among adolescents with intellectual disabilities","volume":"5","author":"Altaye K. Z.","year":"2019","journal-title":"British medical journal Open Sport & Exercise Medicine"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/10611860903318134"},{"key":"e_1_2_2_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.027"},{"key":"e_1_2_2_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.22065"},{"key":"e_1_2_2_8_1","doi-asserted-by":"publisher","DOI":"10.1139\/apnm-2018-0108"},{"key":"e_1_2_2_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33352-3"},{"key":"e_1_2_2_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20230403"},{"key":"e_1_2_2_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0b013e32802b7030"},{"key":"e_1_2_2_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2020.147126"},{"key":"e_1_2_2_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00317.2022"},{"key":"e_1_2_2_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-020-01432-0"},{"key":"e_1_2_2_15_1","doi-asserted-by":"publisher","DOI":"10.1139\/h05-002"},{"key":"e_1_2_2_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.3614"},{"key":"e_1_2_2_17_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.26.061505.111258"},{"key":"e_1_2_2_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.02.006"},{"key":"e_1_2_2_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-019-01889-7"},{"key":"e_1_2_2_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.adh2783"},{"key":"e_1_2_2_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-024-00526-8"},{"key":"e_1_2_2_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep09884"},{"key":"e_1_2_2_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.117774"},{"issue":"6","key":"e_1_2_2_24_1","first-page":"830","article-title":"Exercise intensity and its effects on thyroid hormones","volume":"26","author":"Ciloglu F.","year":"2005","journal-title":"Neuro Endocrinology Letters"},{"key":"e_1_2_2_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/00041433-200402000-00004"},{"key":"e_1_2_2_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13310"},{"key":"e_1_2_2_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12030788"},{"key":"e_1_2_2_28_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-6025fje"},{"key":"e_1_2_2_29_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-8527rev"},{"key":"e_1_2_2_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-024-05860-z"},{"key":"e_1_2_2_31_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.20.5.649"},{"key":"e_1_2_2_32_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.47.10.1613"},{"key":"e_1_2_2_33_1","doi-asserted-by":"publisher","DOI":"10.1385\/JMN:16:1:1"},{"key":"e_1_2_2_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/function\/zqae005"},{"key":"e_1_2_2_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-022-03204-8"},{"key":"e_1_2_2_36_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP273185"},{"key":"e_1_2_2_37_1","doi-asserted-by":"publisher","DOI":"10.1249\/mss.0b013e31802f04c7"},{"key":"e_1_2_2_38_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000049974.74242.C6"},{"key":"e_1_2_2_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.656"},{"key":"e_1_2_2_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15833-5"},{"key":"e_1_2_2_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14061166"},{"key":"e_1_2_2_42_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14354"},{"key":"e_1_2_2_43_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP283582"},{"key":"e_1_2_2_44_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00256.2016"},{"key":"e_1_2_2_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00309.2012"},{"key":"e_1_2_2_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07925"},{"key":"e_1_2_2_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-1981(03)00071-4"},{"key":"e_1_2_2_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-021-00438-z"},{"key":"e_1_2_2_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1474"},{"key":"e_1_2_2_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology11071063"},{"key":"e_1_2_2_51_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-19-0710"},{"key":"e_1_2_2_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci12091143"},{"key":"e_1_2_2_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep43296"},{"issue":"1","key":"e_1_2_2_54_1","first-page":"313","article-title":"Ketone bodies: From enemy to friend and guardian angel","volume":"19","author":"Kolb H.","year":"2021","journal-title":"BioMed Central Medicine [Electronic Resource]"},{"key":"e_1_2_2_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2013.07.015"},{"key":"e_1_2_2_56_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend.11.6.0007"},{"key":"e_1_2_2_57_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14497"},{"key":"e_1_2_2_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-0186(00)00102-9"},{"key":"e_1_2_2_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2016.12.003"},{"key":"e_1_2_2_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0275-4"},{"key":"e_1_2_2_61_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0269fje"},{"key":"e_1_2_2_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2008.09.002"},{"key":"e_1_2_2_63_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-3149fje"},{"key":"e_1_2_2_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12970-018-0234-y"},{"key":"e_1_2_2_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-022-00716-4"},{"key":"e_1_2_2_66_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adh1403"},{"key":"e_1_2_2_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13868"},{"key":"e_1_2_2_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2013.10.006"},{"key":"e_1_2_2_69_1","doi-asserted-by":"publisher","DOI":"10.1515\/teb-2024-0014"},{"key":"e_1_2_2_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2011.04.007"},{"key":"e_1_2_2_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.05.025"},{"key":"e_1_2_2_72_1","article-title":"PPARs: Nuclear receptors controlled by, and controlling, nutrient handling through nuclear and cytosolic signaling","volume":"2010","author":"Moreno M.","year":"2010","journal-title":"Peroxisome Proliferator\u2010Activated Receptor Research"},{"key":"e_1_2_2_73_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113570"},{"key":"e_1_2_2_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.08.032"},{"key":"e_1_2_2_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2014.08.009"},{"key":"e_1_2_2_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46116-y"},{"key":"e_1_2_2_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-14268-w"},{"key":"e_1_2_2_78_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.716594"},{"key":"e_1_2_2_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.04.027"},{"key":"e_1_2_2_80_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glac121"},{"key":"e_1_2_2_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2020.107647"},{"key":"e_1_2_2_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(98)00141-5"},{"key":"e_1_2_2_83_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200010000-00012"},{"key":"e_1_2_2_84_1","doi-asserted-by":"publisher","DOI":"10.3164\/jcbn.19-87"},{"key":"e_1_2_2_85_1","doi-asserted-by":"publisher","DOI":"10.1249\/JES.0000000000000307"},{"key":"e_1_2_2_86_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.199448"},{"key":"e_1_2_2_87_1","doi-asserted-by":"publisher","DOI":"10.1249\/JSR.0000000000000732"},{"key":"e_1_2_2_88_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-111120-111518"},{"key":"e_1_2_2_89_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/620919"},{"key":"e_1_2_2_90_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000002242"},{"key":"e_1_2_2_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.08.105"},{"key":"e_1_2_2_92_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0223024"},{"key":"e_1_2_2_93_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241813845"},{"key":"e_1_2_2_94_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11102368"},{"key":"e_1_2_2_95_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00370-09"},{"key":"e_1_2_2_96_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.15931"},{"key":"e_1_2_2_97_1","article-title":"Neuroprotective mechanisms of ppar\u03b4: Modulation of oxidative stress and inflammatory processes","volume":"2011","author":"Schnegg C. I.","year":"2011","journal-title":"Peroxisome Proliferator\u2010Activated Receptor Research"},{"key":"e_1_2_2_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2017.03.018"},{"key":"e_1_2_2_99_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108057"},{"key":"e_1_2_2_100_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-022-00528-6"},{"key":"e_1_2_2_101_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.15092"},{"key":"e_1_2_2_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2016.06.011"},{"key":"e_1_2_2_103_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20577"},{"key":"e_1_2_2_104_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2005.03.018"},{"key":"e_1_2_2_105_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab333"},{"key":"e_1_2_2_106_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14153145"},{"key":"e_1_2_2_107_1","doi-asserted-by":"publisher","DOI":"10.4103\/cjp.cjp_95_21"},{"key":"e_1_2_2_108_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00447.2021"},{"key":"e_1_2_2_109_1","doi-asserted-by":"publisher","DOI":"10.1139\/apnm-2014-0290"},{"key":"e_1_2_2_110_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.01094"},{"key":"e_1_2_2_111_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep27618"},{"key":"e_1_2_2_112_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00604-023-05878-w"},{"key":"e_1_2_2_113_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01821.x"},{"key":"e_1_2_2_114_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00008.2013"},{"key":"e_1_2_2_115_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.09.008"},{"key":"e_1_2_2_116_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80467-0"},{"key":"e_1_2_2_117_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aau1468"},{"key":"e_1_2_2_118_1","doi-asserted-by":"publisher","DOI":"10.2527\/jas.2009-2597"},{"key":"e_1_2_2_119_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu6072493"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP287462","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP287462","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP287462","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:17:56Z","timestamp":1773818276000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP287462"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,5]]},"references-count":118,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1113\/JP287462"],"URL":"https:\/\/doi.org\/10.1113\/jp287462","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,5]]},"assertion":[{"value":"2024-10-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}